DESCRIPTION (Applicant's Description): The candidate, Dr. Jeffrey Morgan, is now completing training in Hematology-Oncology at Brigham and Women's Hospital and will be promoted to Instructor in Medicine beginning in July, 1996. He is committed to a career in academic medicine, with an emphasis in basic cancer research. He has previously worked in the laboratories of Dr. Eric Kandel and Dr. David Livingston. In the laboratory of his mentor, Dr. Jeffrey Sklar, Chief of the Division of Molecular Oncology in the Department of Pathology, he is now developing the skills necessary to establish himself as an independent investigator. The Sklar laboratory offers an intellectually vital and scientifically diverse environment. Projects include genomic cloning techniques, mutation screening, minimal residual disease detection, somatic hypermutation and a functional analysis of Notch, a signal transducer cloned in the lab, implicated in human T cell lymphoma. In this setting, the extensive intellectual, clinical and laboratory resources of the BWH Pathology Department are accessible to Dr. Morgan. Outside the laboratory and the Department, the Harvard Medical School and Harvard Medical Area offer a wealth of educational opportunities. Courses in immunology and genetics will be undertaken in Years 01 and 02 of this RCA; Years 03 to 05 will see a further intensification of the research experience. In the laboratory, he will focus on the molecular pathogenesis of MALT lymphoma. The t(11;18)(q21;q21) is characteristic of this disease. In preliminary studies, he has identified YACs flanking and spanning this breakpoint. Positional cloning will be used to identify the translocation-associated gene products. Expression of these gene products will be correlated with tumor stage. Finally, models will be developed to facilitate functional analysis.